Year: 2011
Type: article
Abstract: Hodgkin Building, Guys Campus, London SE1 1UL, UK. Drug penetration into the central nervous system (CNS) is severely limited by the presence of the blood-brain barrier (BBB). The BBB is formed by the endothelial cells of the capillaries in brain tissue and also by the epithelial cells of the choroid plexuses, which constitute the blood-cerebrospinal fluid barrier (BSCFB). At both barriers the endothelial and epithelial cells respectively form tight junctions between the cell boundaries which abolishes any aqueous paracellular diffusive pathway between the cells; a pathway which exists in the capillaries of most other tissues. Thus transport of solutes in and out of the brain has to be transcellular across the endothelial cells of the BBB and the epithelial cells of the BSCFB. Solutes may move into the brain passively down a concentration gradient if they are sufficiently lipid soluble to dissolve in the cell membrane, or if polar, such as glucose, amino acids and other essential nutrients they will require the presence of specific transport systems embedded in the cell membranes. Some lipid soluble molecules are actively effluxed from the barriers by ATP-binding cassette (ABC) transporters which transport these solutes out of the brain. Therapeutic drugs entering the CNS are also subject to these processes and the presence of the BBB is a major hurdle to the treatment of most CNS disease. This presentation will consider the relationship of the structure and the function of the CNS barriers, the compartments present in the CNS their relevance to Alzheimer disease and the factors influencing drug penetration into the CNS.
Source: Alzheimer s & Dementia
Author: William Banks
Institution: University of Washington
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4212893647